Description

Estrogen related receptor (ERR gamma), a NR3 Steroid Receptor is an orphan member of the nuclear hormone receptor superfamily. All the ERR family members (1,2, and 3) share an almost identical DNA binding domain, which has 68% amino acid identity with that of estrogen receptor. Studies involving the crystal structure of the LBD have shown a complex between ERR3 and SRC1. ERR gamma has been suggested to affect differentiation of the brain, heart, and kidney. ERR gamma binds as a monomer to an extended half site of the ERRE type (TCAAGGTCA). ERR gamma has been shown to interact with PGC1 alpha and has been implicated in the regulation of mitochondrial energy metabolism. In humans, ERR gamma pre mRNA undergoes extensive alternative splicing at the 5 prime end, yielding at least six mRNA splice variants and two protein isoforms that differ by 23 amino acids in the N terminus. ERR gamma has been shown to be overexpressed in breast tumors, and its expression is correlated with levels of ErbB4, a likely indicator of preferred clinical course. As a result, ERR gamma has been suggested to be a potential biomarker for favorable clinical course and, possibly, hormonal sensitivity, and as a candidate target for therapeutic development.